Plant-derived extracellular vesicles: emerging carriers for ingestible nucleotide delivery

INTRODUCTION: Plant-derived extracellular vesicles (PEVs) have shown significant promise as a novel oral delivery system for nucleotide-based drugs. The successful oral delivery of nucleotide drugs using PEVs paves the way for developing innovative nucleotide delivery systems in terms of inflammatory bowel disease, cancer and metabolic diseases treatment. By utilizing surface and other engineering modifications, PEVs can circumvent the challenges of oral administration posed by the gastrointestinal barrier and enzymatic degradation. AREAS COVERED: This review covers PEVs as oral nucleotide carriers, focusing on their anti-inflammatory, anticancer, and metabolic disease applications. It includes engineered modification methods (ligand, polymer modification, fusion) and nucleotide delivery application. This review searched for keywords using literature retrieval websites such as PubMed, Embase, and Google Scholar. EXPERT OPINION: This review introduces recent advancements of PEV-based technologies focused on ingestible nucleotide delivery, not only contributing valuable theoretical insights but also offering practical guidance for future precision medicine and drug development by PEVs. However, the current existence of regulatory ambiguity and low production efficiency has hindered the clinical translation and large-scale application of PEV-based oral nucleotide delivery systems.